Sergio Tufik

The NoSAS score for screening of sleep-disordered breathing: a derivation and validation study

BACKGROUND Diagnosis of sleep-disordered breathing requires overnight recordings, such as polygraphy or polysomnography. Considering the cost and low availability of these procedures, preselection of patients at high risk is recommended. We aimed to develop a screening tool allowing identification of individuals at risk of sleep-disordered breathing. METHODS We used the participants from the population-based HypnoLaus cohort in Lausanne, Switzerland, who had a clinical assessment and polysomnography at home, to build a clinical score (the NoSAS score) using multiple factor analysis and logistic regression to identify people likely to have clinically significant sleep-disordered breathing. The NoSAS score was externally validated in an independent sleep cohort (EPISONO). We compared its performance to existing screening scores (STOP-Bang and Berlin scores). FINDINGS We used the 2121 participants from the HypnoLaus cohort who were assessed between Sept 1, 2009, and June 30, 2013. The NoSAS score, which ranges from 0 to 17, allocates 4 points for having a neck circumference of more than 40 cm, 3 points for having a body-mass index of 25 kg/m(2) to less than 30 kg/m(2) or 5 points for having a body-mass index of 30 kg/m(2) or more, 2 points for snoring, 4 points for being older than 55 years of age, and 2 points for being male. Using a threshold of 8 points or more, the NoSAS score identified individuals at risk of clinically significant sleep-disordered breathing, with an area under the curve (AUC) of 0·74 (95% CI 0·72-0·76). It showed an even higher performance in the EPISONO cohort, with an AUC of 0·81 (0·77-0·85). The NoSAS score performed significantly better than did the STOP-Bang (AUC 0·67 [95% CI 0·65-0·69]; p<0·0001) and Berlin (0·63 [0·61-0·66]; p<0·0001) scores. INTERPRETATION The NoSAS score is a simple, efficient, and easy to implement score enabling identification of individuals at risk of sleep-disordered breathing. Because of its high discrimination power, the NoSAS score can help clinicians to decide which patients to further investigate with a nocturnal recording. FUNDING Faculty of Biology and Medicine of the University of Lausanne, Lausanne University Hospital, Swiss National Science Foundation, Leenaards Foundation, GlaxoSmithKline, and Vaud Pulmonary League.

Re: Safety and efficacy of testosterone replacement therapy in adolescents with Klinefelter syndrome: A. Mehta, T. Clearman and D. A. Paduch. J Urol 2014; 191: 1527-1531.

Reply by Authors: The comments of Das et al regarding the contribution of the fibers from the superior hypogastric and inferior mesenteric plexus to renal innervation are largely consistent with those reported in the literature and appear generally correct. However, our article focused entirely on evaluation of the autonomic nervous system from the main renal vessels deep into the renal cortex. We did not evaluate the more proximal nerve distribution on the main renal artery because this anatomy is well described in the literature. Indeed, the references cited by Das et al beautifully characterize the autonomic nerve distribution outside the kidney but make no mention of the intrarenal nerve distribution. After an extensive literature search we affirm that the methodology that allowed us to redefine intrarenal anatomy is unique and has never been previously reported. This anatomy is extremely important during catheter based renal denervation for resistant renovascular hypertension. Furthermore, we agree that our work is preliminary and that human anatomical distribution of the renal nerves may vary by gender, body type and anatomical malformations. Further studies with a greater number of cadavers are warranted to confirm our pilot data. Indeed, this limitation was clearly documented in the article.

The interaction of Sjögren’s syndrome, gastroesophagel reflux and sleep

The interaction of Sjögren’s syndrome, gastroesophagel reflux and sleep Departamento de Psicobiologia, Universidade Federal de São Paulo (UNIFESP), Brazil ⇑ Corresponding author. Address: Department of Psychobiology, Universidade Federal de São Paulo, Rua Napoleão de Barros, 925, Vila Clementino – SP 04024-002, São Paulo, Brazil. Tel.: +55 11 2149 0155; fax: +55 11 5572 5092. E-mail address: sergio.tufik@unifesp.br (R. Tufik)

Neuroendocrine Outcomes of Sleep Deprivation in Humans and Animals

Hormones can modulate and be modulated by sleep. This close relationship has been recognised for many decades. Sleep deprivation is an adverse condition that can alter the functioning of the neuroendocrine system, inasmuch as concentrations of hormones involved in anabolic processes, such as growth hormone (GH) are reduced, whilst levels of hormones involved in anabolic processes, such as glucocorticoids (GC) are increased. Therefore, prolonged periods of sleep deprivation, either internally or externally imposed, may lead to a wear and tear phenomenon, much similar to prolonged stressful conditions. In human beings, the vicious circle composed by sleep deprivation, stress and obesity has been claimed to be a major contributor to type II diabetes, cardiovascular diseases and ultimately, death

Sleep restriction during pregnancy and its effects on blood pressure and renal function among female offspring

The influence of sleep restriction (SR) during pregnancy on blood pressure and renal function among female adult offspring was investigated. Pregnant Wistar rats were distributed into control and SR groups. The SR was performed between the 14th and 20th days of pregnancy (multiple platforms method for 20 h/day). At 2 months of age, half of the offspring from both groups were subjected to an ovariectomy (ovx), and the other half underwent sham surgery. The groups were as follows: control sham (Csham), control ovx (Covx), SR sham (SRsham), and SR ovx (SRovx). Renal function markers and systolic blood pressure (BPi, indirect method) were evaluated at 4, 6, and 8 months. Subsequently, the rats were euthanized, kidneys were removed, and processed for morphological analyses of glomerular area (GA), number of glomeruli per mm3 (NG), and kidney mass (KM). Increased BPi was observed in the Covx, SRsham, and SRovx groups compared to Csham at all ages. Increased plasma creatinine concentration and decreased creatinine clearance were observed in the SRsham and SRovx groups compared to the Csham and Covx groups. The SRovx group showed higher BPi and reduced creatinine clearance compared to all other groups. The SRovx group showed reduced values of GA and KM, as well as increased NG, macrophage infiltration, collagen deposit, and ACE1 expression at the renal cortex. Therefore, SR during pregnancy might be an additional risk factor for developing renal dysfunction and increasing BP in female adult offspring. The absence of female hormones exacerbates the changes caused by SR.

Do Naps and Nocturnal Sleep Impact Gastroesophageal Reflux Disease Differently

Reply. Multiple studies have confirmed that chronic abdominal pain (CAP) is the most frequent reason esophagogastroduodenoscopies (EGDs) are being performed in children. The use of EGD for CAP seems to be increasing, along with the number of biopsies performed during EGD. With clinical guidelines suggesting that most children with CAP have functional disorders, we sought to determine if these EGDs are largely unnecessary or if EGDs offer some value in children with CAP. We discovered substantial gaps in the existing evidence. The letter from Dr Mones states that “nighttime wakening is no longer considered an alarm symptom,” however, the Rome III criteria clearly state that “pain that wakes the child from sleep” is an alarm feature. Our study was designed to examine the yield of EGD in CAP, therefore we did not examine the yield of “simple, noninvasive tests.” Dr Mones also suggests noninvasive testing for patients with celiac and inflammatory bowel diseases, however, clinical guidelines state both of these conditions require an EGD. Although the presence of esophagitis orHelicobacter pylori as determined by biopsy specimen is not necessarily believed to cause abdominal pain, the evidence is either limited or inconclusive. Dr Bourke cautions against building multiple endoscopy units based on our study findings. However, there is a flaw in his calculations; our study is not applicable to all children who have CAP. Our study population includes only children with CAP who are referred to a gastroenterologist and selected for an EGD. This would include a small percentage of the total number of children with CAP. We agree that our observational study cannot account for a placebo effect or determine causality. However, our finding of a 38% diagnostic yield is not an exaggeration. Sheiko et al also reported abnormal findings in 35% of EGDs. Our multicenter retrospective analysis of 1190 EGDs confirmed a 38% yield in children referred to a gastroenterologist for CAP. Our message is as follows: more studies are needed to uncover the possible utility of EGD in a subset of children with CAP. By defining this subset, we may be able to better use clinical reasoning, laboratory examinations, and empiric drug adjustment to avoid invasive procedures. We must not be afraid to “challenge long held beliefs and clinical experience suggesting that children with CAP invariably have functional, nonorganic disorders.” The case of eosinophilic esophagitis illustrates that the findings and implications of biopsy specimens taken during EGD can change over time, so we must constantly evaluate our practices and beliefs.

Better Understanding of Bariatric Surgery Outcomes Through Sleep

Dear Editor, According to the World Health Organization, obesity and being overweight represent a global health threat for modern society, being so common that they currently are significant causes of ill-health. In this context, Sanchis and colleagues recently published an interesting longitudinal study evaluating the cardiovascular (CV) risk profile of patients undergoing bariatric surgery [1]. Among the assessed parameters, the authors included an objective evaluation of obstructive sleep apnea syndrome (OSAS), an underdiagnosed condition predisposed by obesity. OSAS is a significant public health problem whose prevalence has been increasing worldwide along with the ongoing epidemic of obesity. In the study by Sanchis et al., OSAS was observed in 30 % of the control group which did not undergo bariatric surgery, corroborating previous data that found a prevalence of OSAS of 32.8 % in the general population [2]. It is interesting to note that the authors found that the percentage of patients with OSAS was much higher (63 %) in the group that had chosen to have bariatric surgery. Apart from diabetes, this was the only significantly obesity-associated comorbidity in the surgery group. These data may be indicative of the various deleterious consequences of OSAS on an individual’s life, such as excessive daytime sleepiness and fatigue, which may make the patient more likely to opt for surgery rather than other interventions, in order to achieve better and faster results. The range of conditions directly affected by OSAS is vast. One of the most examined is blood pressure. It is known that the obstruction of the upper airway is followed by sleep fragmentation, reduced intrathoracic pressure and intermittent hypoxia during sleep [3]. Among other pathways still under investigation, it is believed that these events lead to hypertension through sympathetic activation, systemic inflammation, and endothelial dysfunction [3]. For an even longer period of time, the relationship between OSAS and glucose metabolism has been a subject of interest. Epidemiologic studies of OSAS patients have found a high prevalence of type 2 diabetes, and studies of type 2 diabetics have found a high prevalence of OSAS [4]. Despite the difficulty in establishing causality and consequence in this context, the abovementioned pathophysiology seems to contribute to both pancreatic β-cell dysfunction and widespread insulin resistance [4]. Completing the three main elements of CV risk, dyslipidemia was also found to have a close relation with OSAS, as shown in a recent meta-analysis. Nadeem and colleagues [5] reported that patients with OSAS seem to have increased total cholesterol, low density lipoprotein, and triglyceride blood levels, as well as decreased high-density lipoprotein. They also suggested that these findings are related to decreased androgen levels, also found in OSAS [6]. Last, but not least, sleep fragmentation also plays a major role in patients with OSAS, interfering with eating behavior. A higher energy intake is seen after sleep restriction periods [7], as sleep-deprived subjects tend to go more for high-calorie foods, instead of low-calorie ones [8]. In addition, short sleep duration leads to lower levels of leptin and higher levels of ghrelin [9], a hormonal profile that is likely to increase appetite, which may explain the association between obesity and sleep restriction. S. B. Tufik (*) Medical School, Universidade de São Paulo (USP), SP, São Paulo, Brazil e-mail: tufiksb@gmail.com

Potential role of sleep in bipolar disorder.

Analyzing testosterone levels in suicide attempters is a very prominent approach in understanding the causes that may lead to this terrifying event. In Science, it is very stimulating when we are able to find a single factor or even a few that clearly lead to a certain consequence. However, in many cases, as with suicide in patients with bipolar disorder, there is a more intricate and complex range of factors that act simultaneously. The recent study by Sher et al. (2012) takes an outstanding view in the relationship between testosterone and bipolar disorder and we would like to suggest that a sleep evaluation could give another dimension to this discussion. Sher et al. present an innovative study “Testosterone levels in suicide attempters with bipolar disorder” examining the possibility of a relationship between testosterone levels and the manifestations of bipolar disorder. The study included patients with clinically diagnosed bipolar disorder, with at least one past suicide attempt, analyzing demographic and clinical parameters of this condition. The results show that men present a higher lethality of suicide attempts while women have a higher suicide ideation score. Similar results have been shown by previous studies (Nivoli et al., 2011). For instance, in the most populated Latin-American country, Brazil, approximately 80% of all successful suicide attempts made from 1996 to 2010 were by men. However, the authors observed new findings of a positive correlation between testosterone levels and both the number of manic episodes and the number of suicide attempts. Such an association has never before been related upon, andmay be an important measure to analyze the significance of this hormone in the manic states of bipolar disorder. Although these findings are interesting it certainly raises some debate. Testosterone has been a hormone of great interest for centuries. Aside from the effects on sexual function and aggression mentioned by the authors, testosterone has been proven to have a connection to sleep (as reviewed by Andersen et al., 2008). Indeed, sleep has a great impact on the secretion of testosterone as explored by Andersen et al. that sleep shortage leads to a significant decrease in testosterone blood levels in both animal models and human studies (Leproult and Van Cauter, 2011).